Vitamin D status, vitamin D receptor polymorphisms, and risk of cardiometabolic multimorbidity

Abstract Background The prevalence of cardiometabolic multimorbidity (CMM) has increased substantially in recent years. Previous studies have established the associations between vitamin D, vitamin D receptor (VDR) polymorphisms, and the risk of individual cardiometabolic disease (CMD). However, the...

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Main Authors: Jianhua Ma, Pingan Li, Jinqi Wang, Haiping Zhang, Zhiwei Li, Lixin Tao, Xinghua Yang, Yanxia Luo, Xiuhua Guo, Bo Gao
Format: Article
Language:English
Published: BMC 2025-05-01
Series:Nutrition Journal
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Online Access:https://doi.org/10.1186/s12937-025-01139-z
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author Jianhua Ma
Pingan Li
Jinqi Wang
Haiping Zhang
Zhiwei Li
Lixin Tao
Xinghua Yang
Yanxia Luo
Xiuhua Guo
Bo Gao
author_facet Jianhua Ma
Pingan Li
Jinqi Wang
Haiping Zhang
Zhiwei Li
Lixin Tao
Xinghua Yang
Yanxia Luo
Xiuhua Guo
Bo Gao
author_sort Jianhua Ma
collection DOAJ
description Abstract Background The prevalence of cardiometabolic multimorbidity (CMM) has increased substantially in recent years. Previous studies have established the associations between vitamin D, vitamin D receptor (VDR) polymorphisms, and the risk of individual cardiometabolic disease (CMD). However, the role of these factors in the progression of CMD to CMM or mortality remains unclear. This study aimed to investigate the associations between vitamin D, VDR polymorphisms, and the dynamic progression of CMM, as well as to explore the potential modification effect of VDR polymorphisms. Methods Data for this cohort study were extracted from the UK Biobank. CMM was defined as the coexistence of at least two CMDs, including type 2 diabetes (T2D), coronary heart disease (CHD), and stroke. A multi-state model was used to analyze associations between serum 25(OH)D, VDR polymorphisms and the dynamic progression of CMM. Results The sample included 396,192 participants. Over a median follow-up of 13.8 years, 55,772 individuals experienced at least one CMD and 28,624 died. Compared to participants with 25(OH)D < 25 nmol/L, those with 25(OH)D ≥ 75 nmol/L had HRs of 0.70 (95% CI, 0.67, 0.72) for baseline to first CMD (FCMD), 0.74 (95% CI, 0.67, 0.82) for FCMD to CMM, 0.66 (95% CI, 0.62, 0.70) for baseline to death, 0.84 (95% CI, 0.77, 0.92) for FCMD to death, and 0.85 (95% CI, 0.70, 1.03) for CMM to death. L-shaped relationships of these associations were noted, with a threshold around 45 nmol/L. The rs1544410 (BsmI) T alleles may have a detrimental effect, while the rs11568820 (Cdx2) T alleles may exert a protective effect in the early stages of CMM progression. Additionally, VDR polymorphisms significantly modified the association between serum 25(OH)D and certain stages of CMM progression. Conclusions Maintaining adequate vitamin D levels, as a readily implementable intervention strategy, not only reduces the risk of initial CMD but also delays the progression to CMM or death. Risk stratification based on VDR polymorphisms provides further insights for developing personalized prevention strategies.
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spelling doaj-art-be0ec6f18475426a88ec29fd1e3ea56c2025-08-20T01:52:01ZengBMCNutrition Journal1475-28912025-05-012411910.1186/s12937-025-01139-zVitamin D status, vitamin D receptor polymorphisms, and risk of cardiometabolic multimorbidityJianhua Ma0Pingan Li1Jinqi Wang2Haiping Zhang3Zhiwei Li4Lixin Tao5Xinghua Yang6Yanxia Luo7Xiuhua Guo8Bo Gao9School of Public Health, Capital Medical UniversitySchool of Public Health, Capital Medical UniversitySchool of Public Health, Capital Medical UniversitySchool of Public Health, Capital Medical UniversityNational Clinical Research Center of Cardiovascular Diseases, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical CollegeSchool of Public Health, Capital Medical UniversitySchool of Public Health, Capital Medical UniversitySchool of Public Health, Capital Medical UniversitySchool of Public Health, Capital Medical UniversitySchool of Public Health, Capital Medical UniversityAbstract Background The prevalence of cardiometabolic multimorbidity (CMM) has increased substantially in recent years. Previous studies have established the associations between vitamin D, vitamin D receptor (VDR) polymorphisms, and the risk of individual cardiometabolic disease (CMD). However, the role of these factors in the progression of CMD to CMM or mortality remains unclear. This study aimed to investigate the associations between vitamin D, VDR polymorphisms, and the dynamic progression of CMM, as well as to explore the potential modification effect of VDR polymorphisms. Methods Data for this cohort study were extracted from the UK Biobank. CMM was defined as the coexistence of at least two CMDs, including type 2 diabetes (T2D), coronary heart disease (CHD), and stroke. A multi-state model was used to analyze associations between serum 25(OH)D, VDR polymorphisms and the dynamic progression of CMM. Results The sample included 396,192 participants. Over a median follow-up of 13.8 years, 55,772 individuals experienced at least one CMD and 28,624 died. Compared to participants with 25(OH)D < 25 nmol/L, those with 25(OH)D ≥ 75 nmol/L had HRs of 0.70 (95% CI, 0.67, 0.72) for baseline to first CMD (FCMD), 0.74 (95% CI, 0.67, 0.82) for FCMD to CMM, 0.66 (95% CI, 0.62, 0.70) for baseline to death, 0.84 (95% CI, 0.77, 0.92) for FCMD to death, and 0.85 (95% CI, 0.70, 1.03) for CMM to death. L-shaped relationships of these associations were noted, with a threshold around 45 nmol/L. The rs1544410 (BsmI) T alleles may have a detrimental effect, while the rs11568820 (Cdx2) T alleles may exert a protective effect in the early stages of CMM progression. Additionally, VDR polymorphisms significantly modified the association between serum 25(OH)D and certain stages of CMM progression. Conclusions Maintaining adequate vitamin D levels, as a readily implementable intervention strategy, not only reduces the risk of initial CMD but also delays the progression to CMM or death. Risk stratification based on VDR polymorphisms provides further insights for developing personalized prevention strategies.https://doi.org/10.1186/s12937-025-01139-zVitamin DVitamin D receptor polymorphismsCardiometabolic Multimorbidity
spellingShingle Jianhua Ma
Pingan Li
Jinqi Wang
Haiping Zhang
Zhiwei Li
Lixin Tao
Xinghua Yang
Yanxia Luo
Xiuhua Guo
Bo Gao
Vitamin D status, vitamin D receptor polymorphisms, and risk of cardiometabolic multimorbidity
Nutrition Journal
Vitamin D
Vitamin D receptor polymorphisms
Cardiometabolic Multimorbidity
title Vitamin D status, vitamin D receptor polymorphisms, and risk of cardiometabolic multimorbidity
title_full Vitamin D status, vitamin D receptor polymorphisms, and risk of cardiometabolic multimorbidity
title_fullStr Vitamin D status, vitamin D receptor polymorphisms, and risk of cardiometabolic multimorbidity
title_full_unstemmed Vitamin D status, vitamin D receptor polymorphisms, and risk of cardiometabolic multimorbidity
title_short Vitamin D status, vitamin D receptor polymorphisms, and risk of cardiometabolic multimorbidity
title_sort vitamin d status vitamin d receptor polymorphisms and risk of cardiometabolic multimorbidity
topic Vitamin D
Vitamin D receptor polymorphisms
Cardiometabolic Multimorbidity
url https://doi.org/10.1186/s12937-025-01139-z
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